DESCRIPTION (Adapted from the application): In this Phase I grant application, the researchers propose to synthesize cationic and neutral oligonucleotides to enhance the binding affinity of synthetic oligonucleotides capable of sequence specific triple helix formation which can serve as reagents for directed gene knockout. Triplex-forming oligonucleotides (TFOs) have been shown to inhibit transcription and induce site-specific mutagenesis and recombination in mammalian cells. These reagents can be used as tools for genetic manipulation and have the potential to be developed into gene based therapeutics for cancer, viral infections, and inflammatory diseases. The applicants suggest that the efficiency and binding affinity of triplex targeting can be significantly improved by novel modifications of the oligonucleotides that have been developed in the researcher's laboratories. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE